The invention concerns a method for treating tumors utilizing a combination of known oncolytic agents. The use of the agents together provides unexpectedly greater efficacy than employing the single agents alone.
Cancer chemotherapy has advanced dramatically in recent years. Many tumors can be effectively treated and irradicated utilizing compounds which are either naturally occurring products or synthetic agents. Cancer chemotherapy often entails use of a combination of agents, generally as a means of reducing the toxic effects that are often encountered with the individual agents when used alone.
We have now discovered a unique combination of known oncolytic agents which exhibit a dramatic synergistic effect. The combination utilizes the agent suramin, together with either a vinca alkaloid or estramustine. The combination is especially effective in treating both prostate and breast cancer.
Suramin is the hexasodium salt of a polysulfonated naphthylurea, namely 8,8'-[carbonylbis[imino-3,1-phenylenecarbonylimino(4-methyl-3,1-phenylene) carbonylimine]]bis-1,3,5-naphthalenetrisulfonic acid. It also is known as Germanin, Belgenyl, Maphuride, and Antrypol, hexasodium salt. Suramin has been utilized clinically since the 1920s as an antiparasitic agent, and more recently has been shown to be active in the treatment of metastatic cancer; Stein, et al., J. Clin. Oncology 1989;7(4):499-508. Fruehauf, et al., reported that the antitumor activity of suramin is potentiated by doxorubicin, especially against human prostate cell line PC-3; J. Nat. Can. Inst. 1990;82(14):1206-9. Suramin is known to have several toxic effects in some patients, including adrenal insufficiency, neuropathy, coagulopathy, hypocalcemia, and neurotoxic effects. Occurrence of these adverse effects often requires limiting the dose of suramin, or withdrawing treatment completely.
Several vinca alkaloids are commercially utilized to treat certain cancers. Vinblastine, for example, is an alkaloid isolated from Vinca rosa. Vinblastine sulfate is utilized clinically to treat Hodgkin's disease, lymphocytic lymphoma, histiocytic lymphoma, and breast cancer. Vincristine is another antitumor alkaloid isolated from Vinca rosa. Vindesine is a synthetic derivative of vinblastine. These and other vinca alkaloids are known to have a variety of antineoplastic activities.
Estramustine is an estradiol derivative, namely estradiol 3-bis(2-chloroethyl)carbamate. It is utilized commercially as the phosphate sodium salt, and is indicated in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate.
An object of this invention to provide a method for treating cancers, especially prostate cancer and breast cancer, with a combination comprising suramin together with either a vinca alkaloid or estramustine. A further object is to provide a composition comprising suramin and either a vinca alkaloid or estramustine.